Elena López

Background: COVID-19 pneumonia is associated with significant mortality and has no approved antiviral therapy. Interferon beta1 has shown in vitro studies a potent inhibition of SARS-CoV and MERS-CoV. In an in vitro study, SARS-CoV-2 had more sensitivity to IFN-I pretreatment that SARS-CoV. A combination of IFN beta1b administered subcutaneously with other antiviral treatments has been recommended in several guidelines. However, clinical trial results for the treatment of COVID-19 are pending. We aimed to assess the efficiency of IFN beta1b in COVID19 comparing the in-hospital mortality between patients who received IFN beta1b and patients did not receive. Methods: In this retrospective cohort study, we included hospitalized adults with COVID-19 between February 23th and April 4th, 2020, at the Central Defense Hospital (Madrid, Spain). Subcutaneous interferon beta-1b was recommended in moderate-severe pneumonia. The primary endpoint was in-hospital mortality. Univariate and multivariate analysis was performed to identify variables associated with in-hospital mortality. Findings: We analyzed 256 patients (106 patients in interferon group and 150 patients in control group). At admission, patients who did not receive interferon beta1b presented a greater number of comorbidities. The overall mortality rate was 24.6% (63/256). Twenty-two patients (20.8%) in the interferon group died and 41 (27.3%) in the control group (p=0.229). In the multivariate analysis, the predictors of in-hospital mortality were age, severity of clinical picture at admission and hydroxychloroquine treatment. Interpretation: In hospitalized patients with COVID-19, interferon beta1b treatment was not associated to decrease in-hospital mortality. Further assessment of the earlier administration of this drug in randomized trials is recommended. Funding: none. RESEARCH IN CONTEXT: Evidence before this study: We searched Pubmed on April 27 ^th , 2020, for articles evaluating the efficacy of interferon beta in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the terms: “interferon beta and (COVID-19 or SARS-CoV-2)”. We only found 5 articles. Of them, there was only one original article in English, which was a descriptive study of a case series with solid organ transplant from Spain. Added value of this study: This is the first article that reports the efficacy of interferon beta1b in the treatment of patients with COVID-19. We compared the in-hospital mortality between patients who received interferon beta1b and patients who did not. Patients in both groups received other drugs with a potential antiviral and immunomodulatory effect. There was no significant difference in in-hospital mortality between both groups. Implications of all the available evidence: In our retrospective cohort, treatment with interferon beta1b had not impact on in-hospital survival, however it would be of clinical interest to evaluate the effect of early administration of this drug in the control of SARS-CoV-2 infection in larger randomized clinical trials.

Background: Although no specific treatment for COVID 19 has been proven effective yet, some drugs with in vitro potential against SARS-CoV-2 virus have been proposed for clinical use. Hydroxychloroquine has in vitro anti-viral and immunomodulatory activity, but there is no current clinical evidence of its effectiveness on the outcome of the disease. Methods: We enrolled all 18-85 years old inpatients from Central Defense Hospital, Madrid, Spain, who were hospitalised due to COVID-19 and had a definitive outcome (either dead or discharged). We used a statistical survival analysis. Results: We analysed 220 medical records. 166 patients met the inclusion criteria. 48,8 % of patients not treated with HCQ died, versus 22% in the group of hydroxychloroquine (p=0,002). According to clinical picture at admission, hydroxychloroquine increased the mean cumulative survival in all groups from 1,4 to 1,8 times. This difference was statistically significant in the mild group. Conclusions: in a cohort of 166 patients between 18 to 85 years hospitalised with COVID-19, hydroxychloroquine treatment with an initial loading dose of 800mg improved patient survival when admitted in early stages of the disease. There was a non-statistically significant trend towards survival in all groups, which will need to be clarified in subsequent studies.